Establishment of IPC 227 cells as human xenografts in rabbits: a model of uveal melanoma

Abstract

This study was designed in order to evaluate the feasibility of establishing an animal model of human uveal melanoma. IPC227, a cell line established from the biopsy of a patient with a spindle cell ciliary body melanoma, was transplanted into the anterior chamber of the eye in immunosuppressed New Zealand rabbits. In a second step, a tumour fragment from the anterior chamber was implanted transclerally into the posterior choroid. Complete ophthalmological examinations were then performed on the animals. Characteristic growth patterns were noted depending on the location of implantation. In the anterior chamber, diffuse, flat, heavily pigmented tumours appeared 8 days after the injection of the cell suspension that covered the iris and the angle by day 25, with a success rate of 100%. Nodular, lightly pigmented tumours were obtained 6-7 weeks after subchoroidal implantation, with a 25% success rate. Clinical examination, including fundus photography, ultrasound and magnetic resonance imaging, demonstrated the same characteristics as those of human uveal melanoma, confirming the value of this model for the evaluation of new therapeutic and diagnostic methods in the management of uveal melanoma.

Orthotopic Human Choroidal Melanoma Xenografts in Nude Rats with Aggressive and Nonaggressive PAS Staining Patterns

“…16,17,30 -33,37 We attempted direct injection of a cell suspension into the nude rat suprachoroidal space in an early version of this current model, but leakage from the wound resulted in significant extraocular growth. Another approach has been to grow pieces of human choroidal melanomas in a donor animal and implant them in the suprachoroidal space of an immunosuppressed rabbit 32,34 or nude rat. 18 In two of those studies, the donor tumor was grown subcutaneously, 18,32 whereas in the other it was grown in the anterior chamber.…”

Animal Eye Models for Uveal Melanoma

“…This tumor gave rise to lung metastases but not hepatic metastases. Bonicel et al [46] obtained a 100% success rate of AC inoculation with the IPC 227 cell line, derived from a human ciliary body tumor [47], which was 4-fold more successful than subchoroidal implantation. López-Velasco et al [48] suprachoroidally implanted four human UM cell lines (MKT-BR, OCM1, 92.1, and SP6.5), of which 92.1 and SP6.5 were the most aggressive human cell lines in rabbits as well as the most efficient in getting tumor metastases.…”

Measurement of Human Choroidal Melanoma Xenograft Volume in Rats Using High-Frequency Ultrasound

“…Ultrasound has previously been used to image choroidal melanoma xenografts growing in the immunosuppressed rabbit, 15,16,29 but typically tumors were only imaged at one time point. Recently, a three-dimensional VHF ultrasound system was used to measure tumor volume and ultrasound backscatter in athymic nude mice bearing orthotopic human choroidal melanoma M619 xenografts (Deobhakta AA, et al IOVS 2006; 47:ARVO E-Abstract 4702).…”

“…24 Methods are available to estimate tumor size noninvasively in these models, including fundus photography, 15,16,18 standard ultrasonography, 15,16 and magnetic resonance imaging. 15,25,26 Unfortunately, it is difficult to perform multiple, serial measurements in athymic rodents with these techniques. Given that repeated removal of nude athymic animals from their housing facility is prohibited by most animal investigation committees, all equipment used to monitor growth must be kept in the facility or be easily transportable.…”